Background and purpose
There are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively affects the quality of care for acute cardiovascular conditions. We assessed the impact of ...the COVID-19 outbreak on trends in hospital admissions and workflow parameters of acute stroke care in Amsterdam, The Netherlands.
Methods
We used data from the three hospitals that provide acute stroke care for the Amsterdam region. We compared two 7-week periods: one during the peak of the COVID-19 outbreak (March 16th–May 3th 2020) and one prior to the outbreak (October 21st–December 8th 2019). We included consecutive patients who presented to the emergency departments with a suspected stroke and assessed the change in number of patients as an incidence-rate ratio (IRR) using a Poisson regression analysis. Other outcomes were the IRR for stroke subtypes, change in use of reperfusion therapy, treatment times, and in-hospital complications.
Results
During the COVID-19 period, 309 patients presented with a suspected stroke compared to 407 patients in the pre-COVID-19 period (IRR 0.76 95%CI 0.65–0.88). The proportion of men was higher during the COVID-19 period (59% vs. 47%,
p
< 0.001). There was no change in the proportion of stroke patients treated with intravenous thrombolysis (28% vs. 30%,
p
= 0.58) or endovascular thrombectomy (11% vs 12%,
p
= 0.82) or associated treatment times. Seven patients (all ischemic strokes) were diagnosed with COVID-19.
Conclusion
We observed a 24% decrease in suspected stroke presentations during the COVID-19 outbreak, but no evidence for a decrease in quality of acute stroke care.
Objective
Childhood‐onset systemic lupus erythematosus (SLE) is a severe, lifelong, multisystem autoimmune disease. Long‐term outcome data are limited. This study was undertaken to identify clinical ...characteristics and health‐related quality of life (HRQoL) of adults with childhood‐onset SLE.
Methods
Patients participated in a single study visit comprising a structured history and physical examination. Disease activity (scored using the SLE Disease Activity Index 2000 SLEDAI‐2K), damage (scored using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index SDI), and HRQoL (scored using the Short Form 36 Health Survey) were assessed. Medical records were reviewed.
Results
In total, 111 childhood‐onset SLE patients were included; the median disease duration was 20 years, 91% of patients were female, and 72% were white. Disease activity was low (median SLEDAI‐2K score 4), and 71% of patients received prednisone, hydroxychloroquine (HCQ), and/or other disease‐modifying antirheumatic drugs. The vast majority of new childhood‐onset SLE–related manifestations developed within 2 years of diagnosis. Damage such as myocardial infarctions began occurring after 5 years. Most patients (62%) experienced damage, predominantly in the musculoskeletal, neuropsychiatric, and renal systems. Cerebrovascular accidents, renal transplants, replacement arthroplasties, and myocardial infarctions typically occurred at a young age (median age 20 years, 24 years, 34 years, and 39 years, respectively). Multivariate logistic regression analysis showed that damage accrual was associated with disease duration (odds ratio OR 1.15, P < 0.001), antiphospholipid antibody positivity (OR 3.56, P = 0.026), and hypertension (OR 3.21, P = 0.043). Current HCQ monotherapy was associated with an SDI score of 0 (OR 0.16, P = 0.009). In this cohort, HRQoL was impaired compared to the overall Dutch population. The presence of damage reduced HRQoL scores in 1 domain. High disease activity (SLEDAI‐2K score ≥8) and changes in physical appearance strongly reduced HRQoL scores (in 4 of 8 domains and 7 of 8 domains, respectively).
Conclusion
The majority of adults with childhood‐onset SLE in this large cohort developed significant damage at a young age and had impaired HRQoL without achieving drug‐free remission, illustrating the substantial impact of childhood‐onset SLE on future life.
In a subset of patients, anti tumour necrosis factor (TNF) therapeutic antibodies are immunogenic, resulting in the formation of antidrug antibodies (ADAs). Neutralising ADAs compete with TNF for its ...binding site and reduces the effective serum concentration, causing clinical non-response. It is however unknown to which extent ADAs are neutralising.
To study which proportion of antibodies to human(ised) anti-TNF (adalimumab, golimumab, certolizumab) as well as chimeric anti-TNF (infliximab) is neutralising.
Neutralising capacity of ADAs was assessed using a TNF competition assay in ADA-positive sera of patients treated with adalimumab (n=21), golimumab (n=4), certolizumab (n=9) or infliximab (n=34) sent in to our diagnostic department.
In 34 sera with ADAs to adalimumab, golimumab or certolizumab, >97% of the antibodies were neutralising. In 34 sera with ADAs to infliximab >90% of the antibodies were neutralising. Further characterisation of the broader antibody response to infliximab revealed that non-neutralising antibodies to infliximab do not target murine domains, but may bind infliximab-unique domains not involved in TNF binding (located outside the paratope).
Our study shows that ADAs to human(ised) as well as chimeric anti-TNF therapeutic antibodies are largely neutralising. This highly restricted ADA response suggests an immunodominant role for the paratope of anti-TNF therapeutics.
Proper development of compact myocardium, coronary vessels, and Purkinje fibers depends on the presence of epicardium-derived cells (EPDCs) in embryonic myocardium. We hypothesized that adult human ...EPDCs might partly reactivate their embryonic program when transplanted into ischemic myocardium and improve cardiac performance after myocardial infarction.
EPDCs were isolated from human adult atrial tissue. Myocardial infarction was created in immunodeficient mice, followed by intramyocardial injection of 4x10(5) enhanced green fluorescent protein-labeled EPDCs (2-week survival, n=22; 6-week survival, n=15) or culture medium (n=24 and n=18, respectively). Left ventricular function was assessed with a 9.4T animal MRI unit. Ejection fraction was similar between groups on day 2 but was significantly higher in the EPDC-injected group at 2 weeks (short term), as well as after long-term survival at 6 weeks. End-systolic and end-diastolic volumes were significantly smaller in the EPDC-injected group than in the medium-injected group at all ages evaluated. At 2 weeks, vascularization was significantly increased in the EPDC-treated group, as was wall thickness, a development that might be explained by augmented DNA-damage repair activity in the infarcted area. Immunohistochemical analysis showed massive engraftment of injected EPDCs at 2 weeks, with expression of alpha-smooth muscle actin, von Willebrand factor, sarcoplasmic reticulum Ca2+-ATPase, and voltage-gated sodium channel (alpha-subunit; SCN5a). EPDCs were negative for cardiomyocyte markers. At 6-weeks survival, wall thickness was still increased, but only a few EPDCs could be detected.
After transplantation into ischemic myocardium, adult human EPDCs preserve cardiac function and attenuate ventricular remodeling. Autologous human EPDCs are promising candidates for clinical application in infarcted hearts.
•First complete aerial microbiome inventory through multi-primer metabarcoding.•Huge diversity of bacteria, fungi, protists and plant material in the air.•Microbiome contains many potential pathogens ...of plants and animals.•Many co-occuring taxa such as obligate insect parasites with host insects.•Predictable patterns of microbiome and pathogens depending on weather conditions.
Air is a major conduit for the dispersal of organisms at the local and the global scale. Most research has focused on the dispersal of plants, vertebrates and human disease agents. However, the air represents a key dispersal medium also for bacteria, fungi and protists. Many of those represent potential pathogens of animals and plants and have until now gone largely unrecorded. Here we studied the turnover in composition of the entire aerobiome, the collective diversity of airborne microorganisms. For that we performed daily analyses of all prokaryotes and eukaryotes (including plants) using multi-marker high-throughput sequencing for a total of three weeks. We linked the resulting communities to local weather conditions, to assess determinants of aerobiome composition and distribution. We observed hundreds of microbial taxa, mostly belonging to spore-forming organisms including fungi, but also protists. Additionally, we detected many potential human- and plant-pathogens. Community composition fluctuated on a daily basis and was linked to concurrent weather conditions, particularly air pressure and temperature. Using network analyses, we identified taxonomically diverse groups of organisms with correlated temporal dynamics. In part, this was due to co-variation with environmental conditions, while we could also detect specific host-parasite interactions. This study provides the first full inventory of the aerobiome and identifies putative drivers of its dynamics in terms of taxon composition. This knowledge can help develop early warning systems against pathogens and improve our understanding of microbial dispersal.
Gene products of the major histocompatibility complex (MHC) of human and non-human primates play a crucial role in adaptive immunity, and most of the relevant genes not only show a high degree of ...variability (polymorphism) but also copy number variation (CNV) is observed. Due to this diversity, MHC proteins influence the capability of individuals to cope with various pathogens. MHC and/or MHC-linked gene products such as odorant receptor genes are thought to influence mate choice and reproductive success. Therefore, MHC typing of wild and captive primate populations is considered to be useful in conservation biology, which is, however, often hampered by the need of invasive and time-consuming methods. All intact
Mhc-DRB
genes in primates appear to possess a complex and highly divergent microsatellite, DRB-STR. A panel of 154 pedigreed olive baboons (
Papio anubis
) was examined for their
DRB
content by DRB-STR analysis of genomic DNA. Using the same methodology on DNA of feces samples,
DRB
variability of a silvery gibbon population (
Hylobates moloch
) (
N
= 24), an endangered species, could successfully be studied. In both species, length determination of the DRB-STR resulted in the definition of unique genotyping patterns that appeared to be specific for a certain chromosome. Moreover, the different STR lengths were shown to segregate with the allelic variation of the respective gene. The results obtained expand data gained previously on DRB-STR typing in macaques, great apes, and humans and strengthen the conclusion that this protocol is applicable in molecular ecology, conservation biology, and colony management, especially of endangered primate species.
The subcutaneous implantable cardioverter-defibrillator (S-ICD) and leadless pacemaker (LP) are evolving technologies that do not require intracardiac leads. However, interactions between these two ...devices are unexplored. We investigated the feasibility, safety, and performance of combined LP and S-ICD therapy, considering (i) simultaneous device-programmer communication, (ii) S-ICD rhythm discrimination during LP communication and pacing, and (iii) post-shock LP performance.
The study consists of two parts. Animal experiments: Two sheep were implanted with both an S-ICD and LP (Nanostim, SJM), and the objectives above were tested. Human experience: Follow-up of one S-ICD patient with bilateral subclavian occlusion who received an LP and two LP (all Nanostim, SJM) patients (without S-ICD) who received electrical cardioversion (ECV) are presented. Animal experiments : Simultaneous device-programmer communication was successful, but LP-programmer communication telemetry was temporarily lost (2 ± 2 s) during ventricular fibrillation (VF) induction and 4/54 shocks. Leadless pacemaker communication and pacing did not interfere with S-ICD rhythm discrimination. Additionally, all VF episodes (n = 12/12), including during simultaneous LP pacing, were detected and treated by the S-ICD. Post-shock LP performance was unaltered, and no post-shock device resets or dislodgements were observed (24 S-ICD and 30 external shocks). Human experience : The S-ICD/LP patient showed adequate S-ICD sensing during intrinsic rhythm, nominal, and high-output LP pacing. Two LP patients (without S-ICD) received ECV during follow-up. No impact on performance or LP dislodgements were observed.
Combined LP and S-ICD therapy appears feasible in all animal experiments (n = 2) and in one human subject. No interference in sensing and pacing during intrinsic and paced rhythm was noted in both animal and human subjects. However, induced arrhythmia testing was not performed in the patient. Defibrillation therapy did not seem to affect LP function. More data on safety and performance are needed.
Background: Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. ...One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of infliximab–anti-infliximab complexes. Objective: To investigate the in vivo mechanism of not responding and the role of human anti-chimeric antibodies (HACAs) by using radiolabelled infliximab. Methods: Two responding and two non-responding patients with rheumatoid arthritis, infused with radiolabelled infliximab, were investigated by both imaging and serum analysis. Results: Images showed predominant presence of infliximab in blood up to 24 h, with a trend of faster blood clearance and of higher liver/spleen uptake in a non-responding patient. Clinically inflamed joints showed uptake of the drug. The HACA level in the non-responders was high (1641 and 1008 U/ml), but low or not detectable in responders. Sucrose gradients of serum showed antibody complexes in both non-responders. Various sizes of antibody complexes, including very large ones, were observed in a non-responder who developed a serious infusion reaction. Conclusion: Formation of infliximab–anti-infliximab complexes were found in non-responders due to the presence of large amounts of HACA. This finding, supported by both imaging and serum analysis data, may explain failure of infliximab treatment.
Preoperative embolization (PE) reduces intraoperative blood loss during surgery for spinal metastases of hypervascular primary tumors such as thyroid and renal cell tumors. However, most spinal ...metastases originate from primary breast, prostate, and lung tumors and it remains unclear whether these and other spinal metastases benefit from PE.
To assess the (1) efficacy of PE on the amount of intraoperative blood loss and safety in patients with spinal metastases originating from non–hypervascular primary tumors, and (2) secondary outcomes including perioperative allogeneic blood transfusion, anesthesia time, hospitalization, postoperative complication within 30 days, reoperation, 90-day mortality, and 1-year mortality.
Retrospective propensity-score matched, case-control study at 2 academic tertiary medical centers.
Patients 18 years of age or older undergoing surgery for spinal metastases originating from primary non–thyroid, non–renal cell, and non–hepatocellular tumors between January 1, 2002 and December 31, 2016 were included.
The primary outcomes were estimated amount of intraoperative blood loss and complications attributable to PE, such as neurologic injury, wound infection, thrombosis, or dissection. The secondary outcomes included perioperative allogeneic blood transfusion, anesthesia time, hospitalization, postoperative complication within 30 days, reoperation, 90-day mortality, and 1-year mortality.
In total, 495 patients were identified, of which 54 (11%) underwent PE. After propensity score matching on 21 variables, including primary tumor, number of spinal levels, and surgical treatment, 53 non–PE patients were matched to 53 PE patients. Matching was adequate measured by comparing the matched variables, testing the standardized mean differences (<0.25), and inspecting Kernel density plots. The degree of embolization was noted to be complete, until stasis, or successful in 43 (80%) patients.
Intraoperative blood loss did not differ between both groups with a median blood loss in liters of 0.6 (IQR, 0.4–1.2) for non–PE patients and 0.9 (IQR, 0.6–1.2) for PE patients (p=.32). No complications occurred during embolization or the time between embolization and surgery. No differences were found in terms of the secondary outcomes.
Our data suggest that, although no complications occurred and the embolization procedure can be considered safe, patients with non–hypervascular spinal metastases might not benefit from PE. A larger, prospective study could confirm or refute these study findings and aid in elucidating a subset of spinal metastases that might benefit from PE.
Depression and poor glycemic control: a meta-analytic review of the literature.
P J Lustman ,
R J Anderson ,
K E Freedland ,
M de Groot ,
R M Carney and
R E Clouse
Department of Psychiatry, ...Washington University School of Medicine, and the Department of Veterans Affairs Medical Center,
St Louis, Missouri, USA. lustmanp@psychiatry.wustl.edu
Abstract
OBJECTIVE: Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically
reviewed. Our objective was to determine whether depression is associated with poor glycemic control. RESEARCH DESIGN AND
METHODS: Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association
of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate
effect sizes (ESs), and statistically analyze the collective data. RESULTS: A total of 24 studies satisfied the inclusion
and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001).
The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The
ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and
diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15). CONCLUSIONS:
Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish
the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the
long-term course of diabetes.
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